Studies were directed toward the defining the role of disorders of lymphocyte maturation and of immunoregulatory cell interactions in the pathogenesis of immune dysfunctions. Recombinant DNA technology has been applied to the study of the arrangement and rearrangement of immunoglobulin genes and antigen specific T cell receptor genes in lymphocytic leukemia. Such rearrangement of these genes were used to define the lineage and clonality of T and B cell malignancies as well as to define the causes for the failure of maturation of lymphoid cells in patients with non-T and non-B lymphocytic leukemia. Using a monoclonal antibody, anti-Tac, the human receptor for T cell growth factor (interleukin-2) has been purified to homogeneity. The receptor is a 55,000 dalton glycoprotein composed of a 33,000 dalton peptide backbone that is post-translationally modified by introduction of N and O linked carbohydrates, sialic acid, as well as phosphate and sulfate yielding mature receptors. The gene for this receptor has been cloned and expressed and shown to encode a 251 amino acid polypeptide. The anti-Tac monoclonal inhibits in vitro T cell proliferation induced by antigens, the development of cytotoxic and suppressor cells and as well as B cell immunoglobulin production. Activated B cells were shown to bear the IL-2 receptors. Leukemias of helper T cells (Sezary leukemic cells) are Tac antigen negative. In contrast, the adult T cell leukemia which is associated with the type C retrovirus (human T cell leukemia/lymphoma virus, HTLV) universally displays large numbers of IL-2 receptors on the cell surface. The consistent display of IL-2 receptors which may be aberrant in size on adult T cell leukemic cells may play a role in the uncontrolled growth of these cells. Anti-Tac is evaluated for the therapy of patients with adult T cell leukemia.